title: Equivalent functions for B7.1 and B7.2 costimulation in mediating host resistance to Mycobacterium tuberculosis.
abstract: B7.1 and B7.2 are homologous costimulatory molecules expressed predominantly on antigen-presenting cells (APC). Interaction of these B7 molecules with CD28 and CTLA-4 expressed on T cells is a critical step in T cell activation. Previously, we reported that Mycobacterium tuberculosis infection in the combined absence of B7.1 and B7.2 resulted in impaired host resistance to the pathogen. Despite their structural similarities, the individual contribution of B7.1 and B7.2 to the development of pathogenic T cells in autoimmune diseases and protective T cells in infectious diseases is markedly distinct. In the current study, we therefore examined whether B7.1 and B7.2 have discrete, equivalent, or overlapping functions in mediating host resistance to M. tuberculosis. We found that the individual absence of either B7.1 or B7.2 had no effect on the ability of the host to contain bacterial load in the lungs, recruit immune cells to the lung, generate a Th1 response, or induce a pulmonary granulomatous response. These results indicate that B7.1 and B7.2 molecules have equal ability to mediate host resistance to M. tuberculosis, underscoring the therapeutic utility of individual B7.1 and B7.2 antagonists in treating inflammatory disorders.
authors.affiliation: Department of Medicine, Centre for Emerging Pathogens, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Bhatt
authors.forename: Andrew
authors.initials: A
authors.lastname: Kim
authors.forename: Angela
authors.initials: A
authors.lastname: Kim
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Mathur
authors.forename: Padmini
authors.initials: P
authors.lastname: Salgame
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D018122:B7-1 Antigen / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051940:B7-2 Antigen / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018106:CD28 Antigens / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D016207:Cytokines
keywords: B7.1; B7.2; Costimulation; Granuloma; Mouse; Mycobacterium tuberculosis; Th1